Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
  • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
  • C07D471/04—Ortho-condensed systems

Definitions

• This invention relates to processes for preparing 6,7,8,9-tetrahydro-lH- imidazo[4,5-c]qiJJno-h-4-amines.
• X is selected from the group consisting of alkoxy containing one to about four carbon atoms, alkoxyalkyl wherein the alkoxy moiety contains one to about four carbon atoms and the alkyl moiety contains one to about four carbon atoms, alkylamido wherein the alkyl group contains one to about four carbon atoms, amino, substituted amino wherein the substituent is alkyl or hydroxyalkyi of one to about four carbon atoms, and morpholinoalkyl wherein the alkyl moiety contains one to about four carbon atoms, and
• a 4-amino-6,7,8,9-tetrahydro-lH- imidazo[4,5-c]quinoline of Formula I is provided by reducing a 4-amino-lH- imidazo[4,5-c]quinoline of Formula II.
• the reduction is carried out by suspending or dissolving a compound of Formula II in a strong acid (e.g., trifluoroacetic acid or concentrated sulfuric acid), adding a catalytic amount of platinum (TV) oxide, then subjecting the mixture to hydrogen pressure [25 to 100 psi (1.72 X 10 5 to 6.89 X 10 s Pa)].
• a solvent such as ethanol may be included.
• the reaction is preferably carried out by combining a compound of Formula V with a base, preferably an excess of a tertiary amine base (e.g., a trialkylamine base such as triethyl amine) in a suitable solvent such as dichloromethane and then adding the sulfonyl halide or sulfonic anhydride.
• a base preferably an excess of a tertiary amine base (e.g., a trialkylamine base such as triethyl amine) in a suitable solvent such as dichloromethane and then adding the sulfonyl halide or sulfonic anhydride.
• the addition is preferably carried out in a controlled fashion (e.g., dropwise) and at a reduced temperature (e.g., about 0°C).
• the product can be isolated by conventional methods or it can be carried on without isolation as described below in connection with step (3).
• Reaction Scheme IV wherein R, Ri and R 2 are as defined above, illustrates a process of the invention.
• Compounds of Formula X and methods for their preparation are known and disclosed, e.g., in European Patent Application 90.301776.3, U.S. Pat Nos. 4,689,338 (Gerster), 4,698,348 (Gerster), 4,988,815 (Andre), and 5,389,640 (Gerster) all four patents being incorporated herein by reference.
• a 4-hydrazino-lH-imidazo[4,5- c]quinoline of Formula XI is provided by reacting a 4-chloro-lH-imidazo[4,5- cjquinoline of Formula X with hydrazine.
• the reaction can be carried out by combining a compound of Formula X with an excess of hydrazine and heating if necessary.
• the product can be isolated from the reaction mixture using conventional methods.
• a 6H-imidazo[4,5-c]tetrazolo[l,5- ajquinoline of Formula HI is provided by reacting a 4-hydrazino-lH-imidazo[4,5- cjquinoline of Formula XI with sodium nitrite.
• the reaction can be carried out by combining the compound of Formula XI with sodium nitrite in a suitable solvent (e.g., water) in the presence of an acid (e.g., acetic acid).
• a suitable solvent e.g., water
• an acid e.g., acetic acid
• Step (3) of Reaction Scheme IV can be carried out in the same manner as step (6) of Reaction Scheme H.
• the compounds of Formula I can be used in the form of acid addition salts such as hydrochlorides, dihydrogen sulfates, trihydrogen phosphates, hydrogen nitrates, methane sulfonates and salts of other pharmaceutically acceptable acids.
• Pharmaceutically acceptable acid addition salts of Formula I are generally prepared by reaction of the respective compound with an equimolar amount of a strong acid, preferably an inorganic acid such as hydrochloric, sulfuric or phosphoric acid or an organic acid such as methanesulfonic acid in a polar solvent. Isolation of the salt is facilitated by the addition of a solvent in which the salt is insoluble (e.g., diethyl ether).
• R t substituents are straight chain and branched chain alkyl containing one to about eight carbon atoms and hydroxyalkyi wherein the alkyl moiety contains one to about six carbon atoms.
• the most preferred Ri substituents are 2-methylpropyl and 2-hydroxy-2-methylpropyl.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Nitrogen Condensed Heterocyclic Rings (AREA)
• Other In-Based Heterocyclic Compounds (AREA)

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• 1996
  • 1996-06-21 US US08/669,895 patent/US5693811A/en not_active Expired - Lifetime
  • 1996-10-22 EP EP96936832A patent/EP0912564B1/en not_active Expired - Lifetime
  • 1996-10-22 DK DK96936832T patent/DK0912564T3/da active
  • 1996-10-22 ES ES96936832T patent/ES2185808T3/es not_active Expired - Lifetime
  • 1996-10-22 IL IL12734796A patent/IL127347A/en not_active IP Right Cessation
  • 1996-10-22 JP JP10502897A patent/JP2000512994A/ja not_active Withdrawn
  • 1996-10-22 WO PCT/US1996/016913 patent/WO1997048703A1/en not_active Ceased
  • 1996-10-22 AU AU74658/96A patent/AU717564B2/en not_active Ceased
  • 1996-10-22 NZ NZ333168A patent/NZ333168A/xx unknown
  • 1996-10-22 DE DE69625712T patent/DE69625712T2/de not_active Expired - Fee Related
  • 1996-10-22 PT PT96936832T patent/PT912564E/pt unknown
  • 1996-10-22 CA CA002258262A patent/CA2258262A1/en not_active Abandoned
  • 1996-10-22 AT AT96936832T patent/ATE230744T1/de not_active IP Right Cessation
• 1998
  • 1998-12-18 NO NO19986001A patent/NO315086B1/no unknown

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